Obesity and oocyte quality: Significant implications for ART and Emerging mechanistic insights

2021 ◽  
Author(s):  
Macarena B Gonzalez ◽  
Rebecca L Robker ◽  
Ryan D Rose
Keyword(s):  
Pregnancy Complications ◽  
Maternal Obesity ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Live Birth Rate ◽  
Oocyte Quality ◽  
Reproductive Age ◽  
Developmental Competence ◽  
Obese Women ◽  
Increased Risk

Abstract The prevalence of obesity in adults worldwide, and specifically in women of reproductive age, is concerning given the risks to fertility posed by the increased risk of type 2 diabetes, metabolic syndrome and other non-communicable diseases. Obesity has a multi-systemic impact in female physiology that is characterized by the presence of oxidative stress, lipotoxicity, and the activation of pro-inflammatory pathways, inducing tissue-specific insulin resistance and ultimately conducive to abnormal ovarian function. A higher body mass is linked to Polycystic Ovary Syndrome, dysregulated menstrual cycles, anovulation, and longer time to pregnancy, even in ovulatory women. In the context of ART, compared to women of normal BMI, obese women have worse outcomes in every step of their journey, resulting in reduced success measured as live birth rate. Even after pregnancy is achieved, obese women have a higher chance of miscarriage, gestational diabetes, pregnancy complications, birth defects, and most worryingly, a higher risk of stillbirth and neonatal death. The potential for compounding effects of ART on pregnancy complications and infant morbidities in obese women has not been studied. There is still much debate in the field on whether these poorer outcomes are mainly driven by defects in oocyte quality, abnormal embryo development or an unaccommodating uterine environment, however the clinical evidence to date suggests a combination of all three are responsible. Animal models of maternal obesity shed light on the mechanisms underlaying the effects of obesity on the peri-conception environment, with recent findings pointing to lipotoxicity in the ovarian environment as a key driver of defects in oocytes that have not only reduced developmental competence but long-lasting effects in offspring health.

scholarly journals Obesity induces ovarian inflammation and reduces oocyte quality

Reproduction ◽  
2019 ◽  
Vol 158 (3) ◽  
pp. R79-R90 ◽  
Author(s):  
Alexandria P Snider ◽  
Jennifer R Wood
Keyword(s):  
Oxidative Stress ◽  
Gut Microbiome ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
The United States ◽  
Oocyte Quality ◽  
Developmental Competence ◽  
Estrous Cyclicity ◽  
Cytoplasmic Maturation ◽  
And Oxidative Stress

In the United States, 36.5% of women between the ages of 20 and 39 years are obese. This obesity results in not only metabolic disorders including type II diabetes and cardiovascular disease, but also impaired female fertility. Systemic and tissue-specific chronic inflammation and oxidative stress are common characteristics of obesity. This is also true in the ovary. Several studies have demonstrated that pro-inflammatory cytokines and reactive oxygen species alter estrous cyclicity, steroidogenesis and ovulation. Inflammation and oxidative stress also impair meiotic and cytoplasmic maturation of the oocyte which reduces its developmental competence for fertilization and pre-implantation embryo development. Interestingly, there is recent evidence that obesity- and/or polycystic ovary syndrome (PCOS)-dependent changes to the gut microbiome contributes to ovarian inflammation, steroidogenesis and the expression of mRNAs in the oocyte. However, several gaps remain necessitating future studies to identify inflammation, oxidative stress and gut microbiome mechanisms that reduce ovarian function and oocyte quality.

scholarly journals A new customised placental weight standard redefines the relationship between maternal obesity and extremes of placental size and is more closely associated with pregnancy complications than an existing population standard

2019 ◽  
Vol 11 (4) ◽  
pp. 350-359
Author(s):  
Jacqueline M. Wallace ◽  
Joeleita P. Agard ◽  
Graham W. Horgan
Keyword(s):  
Pregnancy Complications ◽  
Maternal Obesity ◽  
Population Based ◽  
Multiple Regression Model ◽  
Placental Weight ◽  
Morbidly Obese ◽  
Obese Women ◽  
Entire Cohort ◽  
Multiparous Women ◽  
The Difference

AbstractPlacental weight is a valuable indicator of its function, predicting both pregnancy outcome and lifelong health. Population-based centile charts of weight-for-gestational-age and parity are useful for identifying extremes of placental weight but fail to consider maternal size. To address this deficit, a multiple regression model was fitted to derive coefficients for predicting normal placental weight using records from healthy pregnancies of nulliparous/multiparous women of differing height and weight (n = 107,170 deliveries, 37–43 weeks gestation). The difference between actual and predicted placental weight generated a z-score/individual centile for the entire cohort including women with pregnancy complications (n = 121,591). The association between maternal BMI and placental weight extremes defined by the new customised versus population-based standard was investigated by logistic regression, as was the association between low placental weight and pregnancy complications. Underweight women had a greater risk of low placental weight [<10thcentile, OR 1.84 (95% CI 1.66, 2.05)] and obese women had a greater risk of high placental weight [>90th centile, OR 1.98 (95% CI 1.88, 2.10)] using a population standard. After customisation, the risk of high placental weight in obese/morbidly obese women was attenuated [OR 1.17 (95% CI 1.09, 1.25)]/no longer significant, while their risk of low placental weight was 59%–129% higher (P < 0.001). The customised placental weight standard was more closely associated with stillbirth, hypertensive disease, placental abruption and neonatal death than the population standard. Our customised placental weight standard reveals higher risk of relative placental growth restriction leading to lower than expected birthweights in obese women, and a stronger association between low placental weight and pregnancy complications generally. Further, it provides an alternative tool for defining placental weight extremes with implications for the placental programming of chronic disease.

Case 11.1

2014 ◽  
pp. 531-532
Author(s):  
Christine U. Lee ◽  
James F. Glockner
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Polycystic Ovaries ◽  
Endocrine Disorder ◽  
Secondary Amenorrhea ◽  
Increased Risk

28-year-old woman with secondary amenorrhea and hirsutism Axial fat-suppressed 2D SSFP images (Figure 11.1.1) demonstrate multiple follicles arranged in the periphery of the ovaries bilaterally. Polycystic ovary syndrome PCOS is the most common endocrine disorder in women of reproductive age, affecting between 6% and 15%, depending on the criteria used for diagnosis. It typically presents with anovulatory or oligo-ovulatory menstrual cycles leading to oligomenorrhea, polycystic ovaries, and clinical and biochemical hyperandrogenism. PCOS is also associated with increased risk of obesity, insulin resistance, diabetes mellitus, metabolic syndrome, and infertility....

253 OXIDATIVE STRESS MAY IMPAIR OOCYTE QUALITY IN DAIRY COWS OF REPRODUCTIVE AGE WITH A REDUCED ANTRAL FOLLICLE COUNT

2013 ◽  
Vol 25 (1) ◽  
pp. 274 ◽  
Author(s):  
I. Tessaro ◽  
F. Franciosi ◽  
V. Lodde ◽  
D. Corbani ◽  
A. M. Luciano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Antral Follicle ◽  
Oocyte Quality ◽  
Antral Follicle Count ◽  
Oxide System ◽  
Reproductive Age ◽  
Developmental Competence ◽  
Mitochondrial Activity

In dairy cattle, oocytes isolated from ovaries with a reduced antral follicle count (AFC) have a low embryonic developmental competence. This may be related to oxidative stress, as indicated by our recent finding that ovaries with reduced AFC show a defective endothelial nitric oxide synthase/nitric oxide system. To further test this hypothesis, we evaluated whether the poor developmental competence of these oocytes was possibly due 1) to an imbalance of the reduced glutathione (GSH) system, because GSH is the major antioxidant compound stored within the oocyte and protects the zygote and early embryos from oxidative damage, and 2) to reduced mitochondrial activity. Ovaries were obtained from the abattoir, and oocytes were collected from ovaries with reduced AFC, with fewer than 10 follicles of 2 to 6 mm in diameter, and aged-matched controls, with more than 10 follicles of 2 to 6 mm in diameter. Oocyte GSH content was evaluated using the 5,5′-dithio-bis(2-nitrobenzoic acid)-GSH reductase recycling micro-GSH assay before and after in vitro maturation (IVM) in the presence or absence of 100 µM cysteamine, a GSH precursor. At the same time the developmental competence after IVF was assessed. Moreover, the mitochondrial activity during IVM was evaluated in additional oocytes from the two ovarian categories by specific MitoTracker dyes (MitoTracker FM Green and MitoTracker Orange CMTMRos, Invitrogen, Carlsbad, CA, USA) and subsequent image analysis (ImageJ software). All data were analysed by ANOVA followed by Fisher’s least significant differences test, and P-values <0.05 were considered significant. Experiments were repeated at least three times. Oocytes isolated from ovaries with a low AFC had a similar GSH content compared with oocytes isolated from control ovaries (n = 65 and 85, respectively; 4.31 ± 0.41 v. 4.51 ± 0.42 pmol oocyte–1). After IVM, oocytes from ovaries with reduced AFC showed a significantly lower GSH content compared with control oocytes (n = 55 and 65, respectively; 4.36 ± 0.31 v. 6.59 ± 0.39 pmol oocyte–1); however, cysteamine supplementation during IVM induced GSH accumulation similar to the control (n = 80 and 85, respectively; 9.88 ± 0.77 v. 10.45 ± 0.88 pmol oocyte–1). It is interesting that the increase in intracellular GSH content significantly improved the developmental competence of oocytes from ovaries with a reduced AFC (n = 196 and 201, respectively; 20.1 ± 2.9% v. 6.2 ± 1.6%), although the blastocyst rate remained lower than the control either with or without cysteamine (n = 218 and 212, respectively; 33.3 ± 3.8% and 34.2 ± 2.4%). Further, immature oocytes from ovaries with a low AFC showed a reduced mitochondrial membrane potential compared with control oocytes (n = 13 and 18, respectively; 1.74 ± 1.19 v. 2.22 ± 1.72, calculated as the ratio between the fluorescence of active and total mitochondria), whereas at the end of IVM, it declined in both categories at a comparable level (n = 17 and 24, respectively; 1.19 ± 0.10 and 1.30 ± 0.06). Our data confirmed the hypothesis that both the GSH imbalance and defective mitochondrial activity contribute to the limited developmental competence of oocytes from ovaries with a reduced AFC. This work was supported by Dote ricerca applicata-FSE, Regione Lombardia, Italy (VL, IT).

scholarly journals A review of therapeutic options for managing the metabolic aspects of polycystic ovary syndrome

2020 ◽  
Vol 11 ◽  
pp. 204201882093830 ◽  
Author(s):  
Mohammed Altigani Abdalla ◽  
Harshal Deshmukh ◽  
Stephen Atkin ◽  
Thozhukat Sathyapalan
Keyword(s):  
Insulin Resistance ◽  
Weight Loss ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Therapeutic Options ◽  
Reproductive Age ◽  
Obese Women ◽  
Cardiovascular Risk Reduction ◽  
Ovary Syndrome ◽  
Incretin Mimetics

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. Metabolic sequelae associated with PCOS range from insulin resistance to type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Insulin resistance plays a significant role in the pathophysiology of PCOS and it is a reliable marker for cardiometabolic risk. Although insulin sensitising agents such as metformin have been traditionally used for managing metabolic aspects of PCOS, their efficacy is low in terms of weight reduction and cardiovascular risk reduction compared with newer agents such as incretin mimetics and SGLT2 inhibitors. With current pharmaceutical advances, potential therapeutic options have increased, giving patients and clinicians more choices. Incretin mimetics are a promising therapy with a unique metabolic target that could be used widely in the management of PCOS. Likewise, bariatric procedures have become less invasive and result in effective weight loss and the reversal of metabolic morbidities in some patients. Therefore, surgical treatment targeting weight loss becomes increasingly common in the management of obese women with PCOS. Newer emerging therapies, including twincretins, triple GLP-1 agonists, glucagon receptor antagonists and imeglemin, are promising therapeutic options for treating T2DM. Given the similarity of metabolic and pathological features between PCOS and T2DM and the variety of therapeutic options, there is the potential to widen our strategy for treating metabolic disorders in PCOS in parallel with current therapeutic advances. The review was conducted in line with the recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome 2018.

scholarly journals Impact of hypocaloric dietary intervention on ovulation in obese women with PCOS

Reproduction ◽  
2017 ◽  
Vol 153 (1) ◽  
pp. R15-R27 ◽  
Author(s):  
Brittany Y Jarrett ◽  
Marla E Lujan
Keyword(s):  
Weight Loss ◽  
Dietary Intervention ◽  
Polycystic Ovary ◽  
Reproductive Function ◽  
Antral Follicle ◽  
Reproductive Age ◽  
Obese Women ◽  
Dietary Interventions ◽  
Wide Range ◽  
The Impact

Polycystic ovary syndrome (PCOS) is a common cause of ovulatory dysfunction affecting women of reproductive age. Obesity and insulin resistance are thought to potentiate disruptions in antral follicle development that result in chronic anovulation, and as such, have become important therapeutic targets of dietary interventions aimed at weight loss. Caloric restriction has been shown to promote sporadic ovulation in obese women with PCOS, but improvements have occurred across a wide range of patients and little has been garnered about the factors that distinguish responders from non-responders. Further, few studies have evaluated the likelihood for modest weight loss to restore normal ovulatory cyclicity in PCOS. Consensus regarding the impact of dietary intervention on ovulation has been limited by variability in the measures used to characterize and report ovulatory status across studies. In response, this review provides an assessment of the evidence surrounding the effectiveness of hypocaloric dietary intervention to normalize ovulatory function in PCOS. The impact of physiological vs methodological factors on the evaluation of ovulatory status is discussed, and recommendations to strengthen future studies in this area are provided. Ultimately, further research is needed to understand the optimal dietary or lifestyle approaches that promote ovulation and sustained improvements in reproductive function in PCOS.

scholarly journals In vivo oocyte developmental competence is reduced in lean but not in obese superovulated dairy cows after intraovarian administration of IGF1

Reproduction ◽  
2011 ◽  
Vol 142 (1) ◽  
pp. 41-52 ◽  
Author(s):  
Miguel A Velazquez ◽  
Klaus-Gerd Hadeler ◽  
Doris Herrmann ◽  
Wilfried A Kues ◽  
Susanne Ulbrich ◽  
...  
Keyword(s):  
Protein Expression ◽  
Dairy Cows ◽  
Polycystic Ovary ◽  
Plasma Concentrations ◽  
Transcript Abundance ◽  
Developmental Competence ◽  
Obese Women ◽  
Embryo Viability

The present study investigated the role of IGF1 in lactating lean and non-lactating obese dairy cows by injecting 1 μg IGF1 into the ovaries prior to superovulation. This amount of IGF1 has been linked with pregnancy loss in women with the polycystic ovary syndrome (PCOS) and was associated with impaired bovine oocyte competence in vitro. Transcript abundance and protein expression of selected genes involved in apoptosis, glucose metabolism, and the IGF system were analyzed. Plasma concentrations of IGF1 and leptin, and IGF1 in uterine luminal fluid (ULF), were also measured. IGF1 treatment decreased embryo viability in lean cows to the levels observed in obese cows. Obese cows were not affected by IGF1 treatment and showed elevated levels of IGF1 (in both plasma and ULF) and leptin. Blastocysts from lean cows treated with IGF1 showed a higher abundance of SLC2A1 and IGFBP3 transcripts. IGF1 treatment reduced protein expression of tumor protein 53 in blastocysts of lean cows, whereas the opposite was observed in obese cows. IGF1 in plasma and ULF was correlated only in the control groups. Blastocyst transcript abundance of IGF1 receptor and IGFBP3 correlated positively with IGF1 concentrations in both plasma and ULF in lean cows. The detrimental microenvironment created by IGF1 injection in lean cows and the lack of effect in obese cows resemble to a certain extent the situation observed in PCOS patients, where IGF1 bioavailability is increased in normal-weight women but reduced in obese women, suggesting that this bovine model could be useful for studying IGF1 involvement in PCOS.

scholarly journals The Role of Ovarian Sex Steroids in Metabolic Homeostasis, Obesity, and Postmenopausal Breast Cancer: Molecular Mechanisms and Therapeutic Implications

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Viroj Boonyaratanakornkit ◽  
Prangwan Pateetin
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Molecular Mechanisms ◽  
Ovarian Function ◽  
Postmenopausal Breast Cancer ◽  
Cellular Metabolism ◽  
Obese Women ◽  
Therapeutic Implications ◽  
Estrogen Production ◽  
Increased Risk

Obese postmenopausal women have an increased risk of breast cancer and are likely to have a worse prognosis than nonobese postmenopausal women. The cessation of ovarian function after menopause results in withdrawal of ovarian sex steroid hormones, estrogen, and progesterone. Accumulating evidence suggests that the withdrawal of estrogen and progesterone causes homeostasis imbalances, including decreases in insulin sensitivity and leptin secretion and changes in glucose and lipid metabolism, resulting in a total reduction in energy expenditure. Together with a decrease in physical activity and consumption of a high fat diet, these factors significantly contribute to obesity in postmenopausal women. Obesity may contribute to breast cancer development through several mechanisms. Obesity causes localized inflammation, an increase in local estrogen production, and changes in cellular metabolism. In addition, obese women have a higher risk of insulin insensitivity, and an increase in insulin and other growth factor secretion. In this review, we describe our current understanding of the molecular actions of estrogen and progesterone and their contributions to cellular metabolism, obesity, inflammation, and postmenopausal breast cancer. We also discuss how modifications of estrogen and progesterone actions might be used as a therapeutic approach for obesity and postmenopausal breast cancer.

scholarly journals The risk of offspring mood and anxiety disorders in the context of prenatal maternal somatic diseases: a systematic review and meta-analysis

2022 ◽  
Vol 31 ◽  
Author(s):  
Xiayu Gong ◽  
Zhixin Fan ◽  
Hanfang Xu ◽  
Hanzhang Wang ◽  
Ningxi Zeng ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Anxiety Disorders ◽  
Mood Disorders ◽  
Maternal Obesity ◽  
Polycystic Ovary ◽  
Meta Analysis ◽  
Mood And Anxiety Disorders ◽  
Increased Risk ◽  
Somatic Diseases

Abstract Aims The importance of prenatal maternal somatic diseases for offspring mood and anxiety disorders may be overlooked or undervalued. We conducted the first systematic review and meta-analysis assessing the risk of offspring mood and anxiety disorders in the context of prenatal maternal somatic diseases. Methods We screened articles indexed in Embase (including Embase, MEDLINE, PubMed-not-MEDLINE), PsycARTICLES and PsycINFO databases up to August 2021. 21 studies were included. We examined the overall associations between prenatal maternal somatic diseases and offspring mood/anxiety disorders. Analyses were stratified according to maternal somatic diseases and follow-up duration. Results We observed an increased risk of mood and anxiety disorders in the context of prenatal maternal somatic diseases [relative risk (RR) = 1.26; 95% confidence interval (CI) 1.15–1.37, RR = 1.31; 95% CI 1.24–1.38]; maternal obesity(RR = 1.92; 95% CI 1.72–2.11), hypertensive disorders (RR = 1.49; 95% CI 1.11–1.86) and infertility (RR = 1.26, 95% CI 1.14–1.39) were risk factors for mood disorders; maternal polycystic ovary syndrome (RR = 1.61; 95% CI 1.42–1.80), severe obesity (RR = 1.56; 95% CI 1.44–1.68) and moderate obesity (RR = 1.36; 95% CI 1.28–1.44) were risk factors for anxiety disorders. Prenatal maternal somatic diseases increased the risk of mood disorders in childhood and adulthood (RR = 1.71; 95% CI 1.34–2.09/RR = 1.19; 95% CI 1.09–1.30), as well as the risk of anxiety disorders in adulthood (RR = 1.33; 95% CI 1.26–1.41). Conclusion The results indicate that prenatal maternal somatic diseases are associated with offspring mood and anxiety disorders, and that the associations may be long-lasting.

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